A new classification of interphase nuclei based on spatial organizations of chromosome 8 and 21 for t(8;21) (q22;q22) acute myeloid leukemia by three-dimensional fluorescence in situ hybridization

Abstract

Interphase heterogenous chromosomes spatially close to each other are predominantly located near the center of nuclei and are prone to incur translocations. We screened a t(8;21) (q22;q22) acute myeloid leukemia-M2 patient during three phases (post-chemotherapy, remittent stage, and relapse) and a donor of normal karyotype as control by two-(2D) and three-dimensional (3D)-fluorescence in situ hybridization (FISH). Our classification of nuclei (normal, transitional, and malignant nuclei) by 3D-FISH analyses may provide a more precise prognosis than 2D-FISH results, especially for remittent stage sample in our study, in which 2D-FISH findings showed normal results, whereas 3D-FISH results showed extreme abnormalities (normal nuclei 27%, transitional nuclei 36%, malignant nuclei 37%). The relative radial positions (d/R) of chromosomes 8 were similar to d/R of chromosomes 21 for the relapse sample. We classified heterogenous chromosome pairs into close pairs and normal pairs based on their relative distances (d′/(2R)). The centers of close pairs were more internal than normal pairs in nuclei in all samples, and the d/R values of a given-type pairwise heterogenous chromosomes were similar among four samples. Our data demonstrate that the classification of nuclei based on spatial organization of chromosomes by 3D-FISH is reasonable and essential for evaluating acute myeloid leukemia prognosis.